Glycoproteins are important constituents of the cell surface of all mammalian cells, both normal and abnormal, many of which serve as antigens in autologous, syngeneic and xenogeneic immunizations. They have been implicated in many other properties of cells which involve specific recognition and interactions. The main objective of this study is to analyze the surface glycoproteins of cultured cells from malignant melanoma and other tumors. A series of mouse monoclonal antibodies (moAbs) to melanoma, astrocytoma and renal cancer have been prepared, and the antigens recognized by some of these moAbs have been identified and partially characterized. Among the antigens showing relative restriction to malignant melanoma is a glycoprotein with a molecular weight of 130,000. An array of epitopes has been defined on this molecule, and its biosynthesis and processing has been studied. Another antigen of malignant melanoma, which is also found on other cell types, has also been analyzed in detail. In these and other tumor types, a number of the moAb-detected antigens have been shown to be carbohydrate in nature. In colon cancer, these determinants tend to be related to A, B, H and Lewis blood group antigens. Glycolipid antigens also play important roles as antigens in many tumor types. Also under way are more general biochemical studies on the nature of cell surface components of human cells and the significance of variation in their expression for differentiation and malignancy.